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1.
Am J Occup Ther ; 77(1)2023 Jan 01.
Article in English | MEDLINE | ID: mdl-36724789

ABSTRACT

IMPORTANCE: In laboratory settings, dual-tasking is a performance strategy affected by dominance and stroke. However, the volitional use of dual-tasking has not been examined during naturalistic performance of activities of daily living (ADLs). OBJECTIVE: To examine dual-tasking in the context of ADLs and identify whether dominance and stroke influence its use. DESIGN: Cross-sectional, observational. SETTING: Academic medical center. PARTICIPANTS: Forty-three participants with chronic stroke and upper extremity (UE) motor impairment and 19 control participants without stroke. OUTCOMES AND MEASURES: We identified dual-tasking as the performance of dual-object primitives (DOPs), a functional strategy to manage two objects simultaneously. We videotaped participants performing feeding and toothbrushing tasks and identified the initiation and frequency of DOPs. We assessed whether these outcomes were influenced by UE dominance or paresis and whether among participants with stroke these outcomes were influenced by motor impairment (using the Fugl-Meyer Assessment) or cognitive impairment (using the Montreal Cognitive Assessment). RESULTS: DOP initiation was reduced on the nondominant side of control UEs and in the paretic UE of participants with stroke. After DOPs were initiated, however, their frequency was not significantly related to dominance or paresis. Among participants with stroke, DOP initiation but not DOP frequency was influenced by motor impairment, and neither were influenced by cognitive impairment. CONCLUSIONS AND RELEVANCE: The initiation of dual-tasking is curtailed in the nondominant and paretic UEs, extending previous laboratory-based findings to a more naturalistic setting. These results may reflect a demand on neural resources that is exceeded when these limbs are used. What This Article Adds: DOPs, a functional strategy to simultaneously engage two objects during ADLs, could serve as a behavioral marker of dual-tasking in real-world activities, supporting their investigation more broadly. Practicing DOPs in rehabilitation could also train the integration of dual-tasking strategies in activity execution.


Subject(s)
Stroke Rehabilitation , Stroke , Adult , Humans , Activities of Daily Living , Cross-Sectional Studies , Paresis , Recovery of Function , Stroke Rehabilitation/methods , Upper Extremity
2.
Cell Rep ; 21(13): 3833-3845, 2017 12 26.
Article in English | MEDLINE | ID: mdl-29281831

ABSTRACT

Oncogenic mutations in BRAF are believed to initiate serrated colorectal cancers; however, the mechanisms of BRAF-driven colon cancer are unclear. We find that oncogenic BRAF paradoxically suppresses stem cell renewal and instead promotes differentiation. Correspondingly, tumor formation is inefficient in BRAF-driven mouse models of colon cancer. By reducing levels of differentiation via genetic manipulation of either of two distinct differentiation-promoting factors (Smad4 or Cdx2), stem cell activity is restored in BRAFV600E intestines, and the oncogenic capacity of BRAFV600E is amplified. In human patients, we observe that reduced levels of differentiation in normal tissue is associated with increased susceptibility to serrated colon tumors. Together, these findings help resolve the conditions necessary for BRAF-driven colon cancer initiation. Additionally, our results predict that genetic and/or environmental factors that reduce tissue differentiation will increase susceptibility to serrated colon cancer. These findings offer an opportunity to identify susceptible individuals by assessing their tissue-differentiation status.


Subject(s)
Cell Differentiation , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/pathology , Genetic Predisposition to Disease , Proto-Oncogene Proteins B-raf/metabolism , Animals , CDX2 Transcription Factor/metabolism , Carcinogenesis/genetics , Carcinogenesis/pathology , Colorectal Neoplasms/genetics , Disease Models, Animal , Epithelium/metabolism , Epithelium/pathology , Female , Gene Expression Regulation, Neoplastic , Homeostasis , Humans , Intestines/pathology , Male , Mice, Mutant Strains , Smad4 Protein/metabolism , Wnt Signaling Pathway
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